Expression of phosphorylated Stat3, cyclin D₁ and Bcl-xL in extramammary Paget disease

Background: Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D₁). The expression of Stat3, Bcl-xL and cyclin D₁ protein has not been investigated in extramammary Paget disease (EMPD). Objectives: To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D₁ protein in EMPD and to evaluate the relationships among them. Methods: Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D₁ and Bcl-xL. Results: Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D₁ and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D₁ expression and between p-Stat3 and Bcl-xL expression. Conclusions: Our study shows that the expression of p-Stat3, cyclin D ₁ and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.